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Item Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure(Springer Nature, 2023-11-18) Zeamer, Abigail L.; Salive, Marie-Claire; An, Xinming; Beaudoin, Francesca L.; House, Stacey L.; Stevens, Jennifer S.; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Rauch, Scott L.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I., Jr.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Harris, Erica; Pearson, Claire; Peak, David A.; Merchant, Roland C.; Domeier, Robert M.; Rathlev, Niels K.; O’Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Bruce, Steven E.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Bucci, Vanni; Haran, John P.; Emergency Medicine, School of MedicinePatients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.Item Correction: Neural correlates of automatic emotion regulation and their association with suicidal ideation in adolescents during the first 90-days of residential care(Springer Nature, 2024-02-19) Dobbertin, Matthew; Blair, Karina S.; Aloi, Joseph; Bajaj, Sahil; Bashford-Largo, Johannah; Mathur, Avantika; Zhang, Ru; Carollo, Erin; Schwartz, Amanda; Elowsky, Jaimie; Ringle, J. L.; Tyler, Patrick; Blair, R. James; Psychiatry, School of MedicineCorrection to: Translational Psychiatry 10.1038/s41398-023-02723-9, published online 23 January 2024 In this article, the affiliation details for Author Sahil Bajaj were incorrectly given as “Department of Cancer Systems Imaging, MD Anderson Center, South Campus Research Bldg, Houston, TX, USA” but should have been “Department of Cancer Systems Imaging, MD Anderson Cancer Center, Houston, TX, USA” The original article has been corrected.Item High-intensity sweet taste as a predictor of subjective alcohol responses to the ascending limb of an intravenous alcohol prime: an fMRI study(Springer Nature, 2024) Alessi, Jonathan; Dzemidzic, Mario; Benson, Katherine; Chittum, George; Kosobud, Ann; Harezlak, Jaroslaw; Plawecki, Martin H.; O’Connor, Sean J.; Kareken, David A.; Neurology, School of MedicineHigh-intensity sweet-liking has been linked to alcohol use disorder (AUD) risk. However, the neural underpinning of this association is poorly understood. To find a biomarker predictive of AUD, 140 participants (social and heavy drinkers, ages 21-26) underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task and stimulation with high (SucroseHigh)- and low-concentration sucrose, as well as viscosity-matched water. On another day after imaging, and just before free-access intravenous alcohol self-administration, participants experienced a 30 mg% alcohol prime (10 min ascent) using the Computerized Alcohol Infusion System. Principal component analysis (PCA) of subjective responses (SR) to the prime's ascending limb generated enjoyable (SRenjoy) and sedative (SRsed) intoxication components. Another PCA created one component reflective of self-administered alcohol exposure (AE) over 90 min. Component loadings were entered as regressors in a voxel-wise general linear fMRI model, with reward type as a fixed factor. By design, peak prime breath alcohol concentration was similar across participants (29 ± 3.4 mg%). SRenjoy on the prime's ascending limb correlated positively with [SucroseHigh > Water] in the supplementary motor area and right dorsal anterior insula, implicating the salience network. Neither SR component correlated with the brain's response to MID. AE was unrelated to brain reward activation. While these findings do not support a relationship between alcohol self-administration and (1) subjective liking of or (2) regional brain response to an intensely sweet taste, they show that alcohol's enjoyable intoxicating effects on the rising limb correspond with anterior insular and supplementary motor area responses to high-concentration sucrose taste. No such associations were observed with MID despite robust activation in those regions. Insula and supplementary motor area responses to intense sensations relate to a known risk factor for AUD in a way that is not apparent with a secondary (monetary) reward.Item Neural correlates of automatic emotion regulation and their association with suicidal ideation in adolescents during the first 90-days of residential care(Springer Nature, 2024-01-23) Dobbertin, Matthew; Blair, Karina S.; Aloi, Joseph; Bajaj, Sahil; Bashford-Largo, Johannah; Mathur, Avantika; Zhang, Ru; Carollo, Erin; Schwartz, Amanda; Elowsky, Jaimie; Ringle, J. L.; Tyler, Patrick; Blair, R. James; Psychiatry, School of MedicineBackground: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI. Methods: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. Daily reports of SI were collected during the participants' first 90-days in residential care. Participants were presented with a task-fMRI measure of emotion regulation - the Affective Number Stroop task shortly after recruitment. Participants were divided into two groups matched for age, sex and IQ based on whether they demonstrated SI. Results: Participants who demonstrated SI showed increased recruitment of regions including dorsomedial prefrontal cortex/supplemental motor area and parietal cortex during task (congruent and incongruent) relative to view trials in the context of emotional relative to neutral distracters. Conclusions: Participants with SI showed increased recruitment of regions implicated in executive control during the performance of a task indexing automatic emotion regulation. Such data might suggest a relative inefficiency in the recruitment of these regions in individuals with SI.Item Patterns of item nonresponse behaviour to survey questionnaires are systematic and associated with genetic loci(Springer Nature, 2023) Mignogna, Gianmarco; Carey, Caitlin E.; Wedow, Robbee; Baya, Nikolas; Cordioli, Mattia; Pirastu, Nicola; Bellocco, Rino; Fiuza Malerbi, Kathryn; Nivard, Michel G.; Neale, Benjamin M.; Walters, Raymond K.; Ganna, Andrea; Medical and Molecular Genetics, School of MedicineResponse to survey questionnaires is vital for social and behavioural research, and most analyses assume full and accurate response by participants. However, nonresponse is common and impedes proper interpretation and generalizability of results. We examined item nonresponse behaviour across 109 questionnaire items in the UK Biobank (N = 360,628). Phenotypic factor scores for two participant-selected nonresponse answers, 'Prefer not to answer' (PNA) and 'I don't know' (IDK), each predicted participant nonresponse in follow-up surveys (incremental pseudo-R2 = 0.056), even when controlling for education and self-reported health (incremental pseudo-R2 = 0.046). After performing genome-wide association studies of our factors, PNA and IDK were highly genetically correlated with one another (rg = 0.73 (s.e. = 0.03)) and with education (rg,PNA = -0.51 (s.e. = 0.03); rg,IDK = -0.38 (s.e. = 0.02)), health (rg,PNA = 0.51 (s.e. = 0.03); rg,IDK = 0.49 (s.e. = 0.02)) and income (rg,PNA = -0.57 (s.e. = 0.04); rg,IDK = -0.46 (s.e. = 0.02)), with additional unique genetic associations observed for both PNA and IDK (P < 5 × 10-8). We discuss how these associations may bias studies of traits correlated with item nonresponse and demonstrate how this bias may substantially affect genome-wide association studies. While the UK Biobank data are deidentified, we further protected participant privacy by avoiding exploring non-response behaviour to single questions, assuring that no information can be used to associate results with any particular respondents.Item Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study(Springer Nature, 2021) Harnett, Nathaniel G.; van Rooij, Sanne J.H.; Ely, Timothy D.; Lebois, Lauren A.M.; Murty, Vishnu P.; Jovanovic, Tanja; Hill, Sarah B.; Dumornay, Nathalie M.; Merker, Julia B.; Bruce, Steve E.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Lewandowski, Christopher; Hendry, Phyllis L.; Sheikh, Sophia; Storrow, Alan B.; Musey, Paul I., Jr.; Haran, John P.; Jones, Christopher W.; Punches, Brittany E.; Swor, Robert A.; McGrath, Meghan E.; Pascual, Jose L.; Seamon, Mark J.; Mohiuddin, Kamran; Chang, Anna M.; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Rathlev, Niels K.; Sanchez, Leon D.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; Mclean, Samuel; Ressler, Kerry J.; Stevens, Jennifer S.; Emergency Medicine, School of MedicineNeurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.Item Rapid, precise, and reliable measurement of delay discounting using a Bayesian learning algorithm(Nature Publishing group, 2020-07-21) Ahn, Woo-Young; Gu, Hairong; Shen, Yitong; Haines, Nathaniel; Hahn, Hunter A.; Teater, Julie E.; Myung, Jay I.; Pitt, Mark A.; Psychiatry, School of MedicineMachine learning has the potential to facilitate the development of computational methods that improve the measurement of cognitive and mental functioning. In three populations (college students, patients with a substance use disorder, and Amazon Mechanical Turk workers), we evaluated one such method, Bayesian adaptive design optimization (ADO), in the area of delay discounting by comparing its test–retest reliability, precision, and efficiency with that of a conventional staircase method. In all three populations tested, the results showed that ADO led to 0.95 or higher test–retest reliability of the discounting rate within 10–20 trials (under 1–2 min of testing), captured approximately 10% more variance in test–retest reliability, was 3–5 times more precise, and was 3–8 times more efficient than the staircase method. The ADO methodology provides efficient and precise protocols for measuring individual differences in delay discounting.Item Structural covariance of the ventral visual stream predicts posttraumatic intrusion and nightmare symptoms: a multivariate data fusion analysis(Springer Nature, 2022-08-08) Harnett, Nathaniel G.; Finegold, Katherine E.; Lebois, Lauren A.M.; van Rooij, Sanne J.H.; Ely, Timothy D.; Murty, Vishnu P.; Jovanovic, Tanja; Bruce, Steven E.; House, Stacey L.; Beaudoin, Francesca L.; An, Xinming; Zeng, Donglin; Neylan, Thomas C.; Clifford, Gari D.; Linnstaedt, Sarah D.; Germine, Laura T.; Bollen, Kenneth A.; Rauch, Scott L.; Haran, John P.; Storrow, Alan B.; Lewandowski, Christopher; Musey, Paul I.; Hendry, Phyllis L.; Sheikh, Sophia; Jones, Christopher W.; Punches, Brittany E.; Kurz, Michael C.; Swor, Robert A.; Hudak, Lauren A.; Pascual, Jose L.; Seamon, Mark J.; Harris, Erica; Chang, Anna M.; Pearson, Claire; Peak, David A.; Domeier, Robert M.; Rathlev, Niels K.; O'Neil, Brian J.; Sergot, Paulina; Sanchez, Leon D.; Miller, Mark W.; Pietrzak, Robert H.; Joormann, Jutta; Barch, Deanna M.; Pizzagalli, Diego A.; Sheridan, John F.; Harte, Steven E.; Elliott, James M.; Kessler, Ronald C.; Koenen, Karestan C.; McLean, Samuel A.; Nickerson, Lisa D.; Ressler, Kerry J.; Stevens, Jennifer S.; Emergency Medicine, School of MedicineVisual components of trauma memories are often vividly re-experienced by survivors with deleterious consequences for normal function. Neuroimaging research on trauma has primarily focused on threat-processing circuitry as core to trauma-related dysfunction. Conversely, limited attention has been given to visual circuitry which may be particularly relevant to posttraumatic stress disorder (PTSD). Prior work suggests that the ventral visual stream is directly related to the cognitive and affective disturbances observed in PTSD and may be predictive of later symptom expression. The present study used multimodal magnetic resonance imaging data (n = 278) collected two weeks after trauma exposure from the AURORA study, a longitudinal, multisite investigation of adverse posttraumatic neuropsychiatric sequelae. Indices of gray and white matter were combined using data fusion to identify a structural covariance network (SCN) of the ventral visual stream 2 weeks after trauma. Participant's loadings on the SCN were positively associated with both intrusion symptoms and intensity of nightmares. Further, SCN loadings moderated connectivity between a previously observed amygdala-hippocampal functional covariance network and the inferior temporal gyrus. Follow-up MRI data at 6 months showed an inverse relationship between SCN loadings and negative alterations in cognition in mood. Further, individuals who showed decreased strength of the SCN between 2 weeks and 6 months had generally higher PTSD symptom severity over time. The present findings highlight a role for structural integrity of the ventral visual stream in the development of PTSD. The ventral visual stream may be particularly important for the consolidation or retrieval of trauma memories and may contribute to efficient reactivation of visual components of the trauma memory, thereby exacerbating PTSD symptoms. Potentially chronic engagement of the network may lead to reduced structural integrity which becomes a risk factor for lasting PTSD symptoms.Item The paucity of morality in everyday talk(Springer Nature, 2023-04-12) Atari, Mohammad; Mehl, Matthias R.; Graham, Jesse; Doris, John M.; Schwarz, Norbert; Davani, Aida Mostafazadeh; Omrani, Ali; Kennedy, Brendan; Gonzalez, Elaine; Jafarzadeh, Nikki; Hussain, Alyzeh; Mirinjian, Arineh; Madden, Annabelle; Bhatia, Rhea; Burch, Alexander; Harlan, Allison; Sbarra, David A.; Raison, Charles L.; Moseley, Suzanne A.; Polsinelli, Angelina J.; Dehghani, Morteza; Neurology, School of MedicineGiven its centrality in scholarly and popular discourse, morality should be expected to figure prominently in everyday talk. We test this expectation by examining the frequency of moral content in three contexts, using three methods: (a) Participants’ subjective frequency estimates (N = 581); (b) Human content analysis of unobtrusively recorded in-person interactions (N = 542 participants; n = 50,961 observations); and (c) Computational content analysis of Facebook posts (N = 3822 participants; n = 111,886 observations). In their self-reports, participants estimated that 21.5% of their interactions touched on morality (Study 1), but objectively, only 4.7% of recorded conversational samples (Study 2) and 2.2% of Facebook posts (Study 3) contained moral content. Collectively, these findings suggest that morality may be far less prominent in everyday life than scholarly and popular discourse, and laypeople, presume.Item Using naltrexone to validate a human laboratory test system to screen new medications for alcoholism (TESMA)- a randomized clinical trial(Springer Nature, 2023-04-05) Spreer, Maik; Grählert, Xina; Klut, Ina-Maria; Al Hamdan, Feras; Sommer, Wolfgang H.; Plawecki, Martin H.; O’Connor, Sean; Böttcher, Michael; Sauer, Cathrin; Smolka, Michael N.; Zimmermann, Ulrich S.; Psychiatry, School of MedicineThis registered clinical trial sought to validate a laboratory test system devised to screen medications for alcoholism treatment (TESMA) under different contingencies of alcohol reinforcement. Forty-six nondependent, but at least medium-risk drinkers were given the opportunity to earn intravenous infusions of ethanol, or saline, as rewards for work in a progressive-ratio paradigm. Work demand pattern and alcohol exposure dynamics were devised to achieve a gradual shift from low-demand work for alcohol (WFA) permitting quickly increasing breath alcohol concentrations (BrAC) to high-demand WFA, which could only decelerate an inevitable decrease of the previously earned BrAC. Thereby, the reward contingency changed, modeling different drinking motivations. The experiment was repeated after at least 7 days of randomized, double-blinded treatment with naltrexone, escalated to 50 mg/d, or placebo. Subjects treated with naltrexone reduced their cumulative WFA (cWFA) slightly more than participants receiving placebo. This difference was not statistically significant in the preplanned analysis of the entire 150 min of self-administration, i.e., our primary endpoint (p = 0.471, Cohen's d = 0.215). Naltrexone serum levels correlated with change in cWFA (r = -0.53; p = 0.014). Separate exploratory analyses revealed that naltrexone significantly reduced WFA during the first, but not the second half of the experiment (Cohen's d = 0.643 and 0.14, respectively). Phase-dependent associations of WFA with changes in subjective stimulation, wellbeing and desire for alcohol suggested that the predominant reinforcement of WFA was positive during the first phase only, and might have been negative during the second. We conclude that the TESMA is a safe and practical method. It bears the potential to quickly and efficiently screen new drugs for their efficacy to attenuate positively reinforced alcohol consumption. It possibly also provides a condition of negative reinforcement, and for the first time provides experimental evidence suggesting that naltrexone's effect might depend on reward contingency.